The new NIA and Alzheimer's Association guidelines for the pre-clinical and mild cognitive impairment (MCI) phase of Alzheimer's disease (AD) place an unprecedented emphasis on biomarkers of AD-pathophysiology (AD-P). The Mayo Clinic Study of Aging (MCSA; U01 AG006786) has longitudinally followed over 2000 individuals aged 70-89 at baseline and recruited from a population-based sample. Amyloid biomarkers (i.e. cerebrospinal fluid (CSF) amyloid and PIB-PET) and biomarkers of neuronal injury (i.e., fluorodeoxyglucose (FDG) PET, quantitative MRI, and CSF tau) have been collected from many individuals. The relationship between these AD-P markers and cognitive change is ongoing. However, because AD-P may begin decades before the emergence of clinical symptoms, it is important to examine these biomarkers in a younger, population-based cohort (i.e. aged 60-69 years). Further, while these CSF and neuroimaging biomarkers may be important for a diagnosis of pre-clinical AD, they will not be ideal for first-line screening of individuals at ris of AD at the population level because of cost, practicality, invasiveness, and patient burden. Thus, the overall goal of this revision is to use the infrastructure of the MCSA to begin establishing a younger population-based sample of persons aged 60-69, collect AD-P biomarkers on these individuals, and to compare two computerized cognitive tests (CogState and CANTAB PAL) as a possible first-line screen for AD-P in both the younger and existing older cohorts. If one of the computerized test is found to be acceptable to participants and feasible on a large scale, it could be used to identify who should have more extensive pen-and-pencil neuropsychological (NP) testing, and more invasive and expensive CSF and neuroimaging biomarker evaluations. We propose the following specific aims. Aim 1: In the new population-based cohort of 420 individuals aged 60-69 years: a) to investigate recruitment rates and the feasibility and acceptability of administering CogState (Brief Battery and CPAL) and the CANTAB PAL at 0, 6 and 12 months; b) to investigate the cross-sectional and longitudinal relationship between CogState, CANTAB PAL and the standard NP battery and MCI status; and c) to compare the cross-sectional correlations between CogState, CANTAB PAL, NP tests, and AD-P neuroimaging markers (MRI, FDG PET, PiB-PET imaging) in a subset of 100 individuals. Aim 2: In a subset of 300 individuals in the established MCSA older cohort, aged 70-89 years: a) to investigate the feasibility and acceptability of administering CogState (Brief Battery and CPAL) and the CANTAB PAL at 0, 6 and 12 months; b) to investigate the cross-sectional and longitudinal relationship between CogState, CANTAB PAL and the standard NP battery and MCI status; and c) to compare the cross- sectional correlations between CogState, CANTAB PAL, NP tests, and AD-P markers (MRI, FDG PET, PiB- PET imaging, CSF amyloid and tau) among subjects with available data. PUBLIC HEALTH RELEVANCE: Alzheimer's disease pathology (AD-P) begins many years before the first symptoms appear. The overall goal of this revision is to use the infrastructure of the Mayo Clinic Study of Aging to begin establishing a younger population-based sample of persons aged 60-69 and to test a brief, computerized test as a possible first-line screen for AD-P in a future, larger cohort. If the computerized test is found to be acceptable to participants an feasible on a large scale, it could be used to identify who should have more extensive cognitive testing, and more invasive and expensive CSF and neuroimaging biomarker evaluations.